A family of fatty acid transporters conserved from Mycobacterium to man
A family of fatty acid transporters conserved from Mycobacterium to man
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DOI：
10.1073/pnas.95.15.8625
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发表时间：
1998-07-21
影响因子：
11.1
通讯作者：
Lodish, HF
中科院分区：
文献类型：
--
作者：
Hirsch, D;Stahl, A;Lodish, HF
长链脂肪酸（LCFA）是大多数生物体的重要能量来源。它们还作为血液激素发挥作用，调节关键的代谢功能，如肝葡萄糖产生。尽管LCFA可以通过质膜的疏水核心扩散到细胞中，但这种非特异性转运不能解释LCFA的高亲和力和特异性转运，所述转运由细胞如心肌、肝细胞和脂肪细胞表现出，脂肪酸转运蛋白（FATP）促进LCFA跨质膜转运，FATP是一种在培养的哺乳动物细胞中表达时增加LCFA摄取的质膜蛋白[Schaffer，J. E.和洛迪什，H。F.（1994）Cell 79，427-436]。在此，我们报道了四种新的鼠FATP的鉴定，其中一种仅在肝脏中表达，另一种仅在肝脏和肾脏中表达。当在哺乳动物细胞中表达时，这两个基因都增加脂肪酸摄取。除了第六个FATP基因之外，所有五个鼠FATP在人类中具有同源物。FATP存在于多种生物体中，如红足东方鲀、秀丽隐杆线虫、黑腹果蝇、酿酒酵母和结核分枝杆菌。FATP基因家族的功能在整个进化过程中是保守的，如C。当在COS细胞或大肠杆菌中过表达时，线虫和分枝杆菌FATP分别促进LCFA摄取。这种进化保守的脂肪酸转运蛋白家族的鉴定将使我们能够更好地了解LCFA穿越脂质双层的机制，并深入了解糖尿病和肥胖症等疾病中能量稳态的控制及其失调。
Long chain fatty acids (LCFAs) are an important source of energy for most organisms. They also function as blood hormones, regulating key metabolic functions such as hepatic glucose production, Although LCFAs can diffuse through the hydrophobic core of the plasma membrane into cells, this nonspecific transport cannot account for the high affinity and specific transport of LCFAs exhibited by cells such as cardiac muscle, hepatocytes, and adipocytes, Transport of LCFAs across the plasma membrane is facilitated by fatty acid transport protein (FATP), a plasma membrane protein that increases LCFA uptake when expressed in cultured mammalian cells [Schaffer, J. E. & Lodish, H. F. (1994) Cell 79, 427-436], Here, we report the identification of four novel murine FATPs, one of which is expressed exclusively in liver and another only in liver and kidney. Both genes increase fatty acid uptake when expressed in mammalian cells, All five murine FATPs have homologues in humans in addition to a sixth FATP gene. FATPs are found in such diverse organisms as Fugu rubripes, Caenorhabditis elegans, Drosophila melanogaster, Saccharomyces cerevisiae, and Mycobacterium tuberculosis. The function of the FATP gene family is conserved throughout evolution as the C. elegans and mycobacterial FATPs facilitate LCFA uptake when overexpressed in COS cells or Escherichia coli, respectively. The identification of this evolutionary conserved fatty acid trans porter family will allow us to gain a better understanding of the mechanisms whereby LCFAs traverse the lipid bilayer as well as yield insight into the control of energy homeostasis and its dysregulation in diseases such as diabetes and obesity.